WO2003090744A1 - Antibacterial compositions comprising metal phthalocyanine analogues - Google Patents
Antibacterial compositions comprising metal phthalocyanine analogues Download PDFInfo
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- WO2003090744A1 WO2003090744A1 PCT/EP2003/004080 EP0304080W WO03090744A1 WO 2003090744 A1 WO2003090744 A1 WO 2003090744A1 EP 0304080 W EP0304080 W EP 0304080W WO 03090744 A1 WO03090744 A1 WO 03090744A1
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- WIPO (PCT)
- Prior art keywords
- phthalocyanine
- compound
- zinc
- tetra
- group
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- 0 Cc1ccc(*)cc1 Chemical compound Cc1ccc(*)cc1 0.000 description 3
- TVSMLBGFGKLKOO-UHFFFAOYSA-N CC1CCN(C)CC1 Chemical compound CC1CCN(C)CC1 TVSMLBGFGKLKOO-UHFFFAOYSA-N 0.000 description 1
- MPUIJCPHOVBPOB-UHFFFAOYSA-N Cc1c[n+](C)ccc1 Chemical compound Cc1c[n+](C)ccc1 MPUIJCPHOVBPOB-UHFFFAOYSA-N 0.000 description 1
- IZPNVUYQWBZYEA-UHFFFAOYSA-N Cc1cc[n+](C)cc1 Chemical compound Cc1cc[n+](C)cc1 IZPNVUYQWBZYEA-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/315—Zinc compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/695—Silicon compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/045—Special non-pigmentary uses, e.g. catalyst, photosensitisers of phthalocyanine dyes or pigments
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/08—Preparation from other phthalocyanine compounds, e.g. cobaltphthalocyanineamine complex
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention relates to pharmaceutical compositions comprising the metal phthalocyanine analogues of formula (I) hereinafter reported and metal chelating compounds, having a good bioavailability and enhanced photodynamic properties, useful for the treatment of infectious diseases and for in vivolex vivo applications.
- metal chelating compounds having a good bioavailability and enhanced photodynamic properties, useful for the treatment of infectious diseases and for in vivolex vivo applications.
- phthalocyanines are molecules able to produce singlet oxygen in good yields as a result of light irradiation and have therefore photoenhanced biocidal activity. The biocidal properties of such molecules, once properly directed, make these molecules extremely interesting for therapeutic applications.
- Zn(ll)-phthalocyanines and other metal-phthalocyanines having applications in photodynamic therapy (PDT) and diagnosis, have been recently described in the US Patent No.
- non cationic compounds having either a porphyrin or a phthalocyanine nucleus, do not show any efficacy against Gram negative unless administered in the presence of additional substances capable of altering the permeability of the outer membrane; Ca 2+ salts, Tris-EDTA, etc., have been used to this aim.
- metal chelating agents in particular metal chelating agents naving specificity for the Ca 2+ and Mg 2+ ions, such as 1 ,2-diaminocyclohexane- N,N,N',N'-tetraacetic acid (CDTA), diethylenetriamine-pentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA).
- compositions comprising at least a metal phthalocyanine analogue of formula (I)
- n O, 1 or 2;
- M is chosen in the; group consisting of Zn, Si(OR 3 ) 2 and AIOR 3 wherein R 3 is chosen in the group, consisting of H and C ⁇ . ⁇ 5 alkyl; R is chosen from H and W, wherein W is represented by the group (X) P R 4 , wherein:
- X is preferably chosen in the group consisting of O, S, -NR and -CH 2 -; and R is
- Y is chosen in the group consisting of C O alkyl and phenyl, possibly substituted, or it forms with the Z group, to which it is bound, a saturated or unsaturated heterocycle, possibly substituted, which may contain up to two heteroatoms chosen in the group consisting of N, O and S;
- Z is chosen in the group consisting of -N, -CH 2 N and -CONHCH 2 CH 2 N; R 5 and R ⁇ , equal or different from one another, are chosen in the group consisting of C ⁇ .
- R and R 8 equal or different from one another, are chosen in the group consisting of H and C ⁇ .
- 15 alkyl ; m, n, p, s, t and u, independently from one another, are 0 or 1 ; and
- v is an integer comprised between 1 and 3;
- Ri and R 2 are chosen from H, W and K, wherein W is as defined above, and K is selected from the group consisting of -
- R 2 is in the position 1(4) or 2(3); in combination with at least a metal chelating agent.
- Figure 1 shows the variation of CFU (colony forming units) of E. co// ATCC 25922 (Log CFU) vs. concentration ( ⁇ M) of the compound ⁇ 2,3,9,10,16,17,23,24-octa[3-
- compound 1 when a population of 6.6x10 6 CFU in
- Figure 2 shows the variation of CFU of E. coli ATCC 25922 (Log CFU) vs. concentration ( ⁇ M) of the formulation according to the invention comprising the compound 1 in combination with EDTA 0.5 mM, when a population of 1.0x10 7 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- Figure 2a shows the variation of CFU of E. coli ATCC 25922 (Log CFU) vs. concentration ( ⁇ M) of the formulation according to the invention comprising the compound 1 in combination with CDTA 0.5 ⁇ M, when a population of 6.6x10 6 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- Figure 2b shows the variation of CFU of E. coli ATCC 25922 (Log CFU) vs. concentration ( ⁇ M) of the formulation according to the invention comprising the compound 1 in combination with DTPA 0.5 mM, when a population of 3.3x10 6 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- Figure 3 shows the variation of CFU of Pseudomonas aeruginosa PAO-1 (Log
- Figure 3a shows the variation of CFU of P. aeruginosa PAO-1 (Log CFU) vs. concentration ( ⁇ M) of the present formulation comprising the compound 1 in combination with EDTA 0.5 mM, when a population of 6.6x10 6 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- Figure 3b shows the variation of CFU of P. aeruginosa PAO-1 (Log CFU) vs. concentration ( ⁇ M) of the formulation of the invention comprising the compound 1 in combination with CDTA 0.5 mM, when a population of 6.6x10 6 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- Figure 3c shows the variation of CFU of P. aeruginosa PAO-1 (Log CFU) vs. concentration ( ⁇ M) of the present formulation comprising the compound 1 in combination with DTPA 0.5 mM, when a population of 6.6x10 6 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- Figure 4 shows the variation of CFU of P. aeruginosa PAO-1 (Log CFU) vs. concentration ( ⁇ M) of the present formulation comprising the compound 1 in combination with EDTA 0.5 mM, at different irradiation times with 50 mW/cm 2 of red light, when a population of 1.0x10 7 CFU in 100 ⁇ L is incubated with the above said formulation.
- Figure 5 shows the variation of CFU of E. coli ATCC 25922 (Log CFU) vs. concentration ( ⁇ M) of the present formulation comprising the compound
- compound 2 ⁇ 2(3),9(10),16(17),23(24)-tetra[1 ,3-ib/s-(trimethylammonium)propyl-2-oxy] zinc(ll) hthalocyanine ⁇ octaiodide (hereinafter referred to as "compound 2”) in combination with EDTA 0.5 mM, when a population of 6.6x10 6 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- Figure 5a shows the variation of CFU of E. coli ATCC 25922 (Log CFU) vs. concentration ( ⁇ M) of the present formulation comprising the compound 2, when a population of 1.0x10 7 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- Figure 6 shows the variation of CFU of P. aeruginosa PAO-1 (Log CFU) vs. concentration ( ⁇ M) of a formulation comprising the compound 1 in combination with polymixine B sulphate 50 mM, at different irradiation times with 50 mW/cm 2 of red light, when a population of 1.0x10 7 CFU in 100 ⁇ L is incubated for 5 minutes with the above said formulation.
- the present invention allows to provide novel pharmaceutical compositions directed to the inactivation of Gram negative bacteria with enhanced physical- chemical and photodynamic properties thanks to the combination of the metal phthalocyanine analogues of formula (I) as above defined with at least a metal chelating agent.
- suitable linker is intended in the sense commonly given to this definition in the field of protein and nucleic acid modification (S.S. Wang, Chemistry of Protein Conjugation and Cross-linking CRC Press Inc. 1993, G.T. Hermanson Bioconjugate Techniques Academic Press, 1996), i.e. an aliphatic moiety which acts as a spacer between the phthalocyanine nucleus and the biological macromolecules, in order to satisfy the desired sterical and/or structural requirements.
- saturated or unsaturated heterocycle possibly substituted the following are preferably meant : morpholine, piperidine, pyridine, pyrimidine, piperazine, pyrrolidine, pyrroline, imidazole, aniline, and julolidine (2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-//]quinoline).
- the preferred products are those in which the group (X) P R includes substituents bearing tertiary or quaternary nitrogen.
- the said group (X) P R 4 is preferably represented by:
- the metal phthalocyanine analogues to be used in combination with metal chelating agents in the pharmaceutical compositions of the invention are defined by the following formulas:
- salts of the phthalocyanine compounds of the present invention include conventional acid addition salts, obtained by the addition of HCI, H 3 PO 4 , H 2 S0 4 , HBr, etc. Additionally, salts obtained by reaction of the carboxylic function or acid groups within the phthalocyanine ring are within the scope of the present invention. Such salts include, for example, salts of carboxylic and sulfonic acid with amine derivatives, basic amino acids and inorganic bases.
- the phthalocyanine compounds of the present invention can be prepared according to reaction schemes that are known in organic chemistry.
- the present compounds of formula (I) included in the cases d) and f) may be prepared as described in US Patent No. 5,965,598, which we incorporate herewith by reference; whereas the present compounds of formula (I) included in cases c), e) and g) may be prepared as described in the International Patent Application No. PCT/EP02/03108, which we incorporate herewith by reference; the present compounds of formula (I) of cases a) and b) may be prepared as described in the European Patent Application No. EP 00112654.9, which we incorporate herewith by reference.
- the phthalocyanine compounds indicated above as compounds 1-24 have been already disclosed in the above said Patent Applications, whereas the compounds indicated above as compounds 25-33 have been newly prepared as described in the following examples.
- the present compositions comprise at least a metal chelating agent, preferably selected from the metal chelating agents having specificity for the Ca 2+ and Mg 2+ ions, such as 1 ,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA), diethylenetriamine-pentaacetic acid (DTPA), ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA), and salts thereof.
- a metal chelating agent preferably selected from the metal chelating agents having specificity for the Ca 2+ and Mg 2+ ions, such as 1 ,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA), diethylenetriamine-penta
- compositions according to the invention are those comprising
- Photodynamic therapy using the phthalocyanine compounds formulated with the compound described in the present invention has a number of advantages.
- the phthalocyanine compounds themselves are minimally toxic in the unexcited state.
- Each phthalocyanine molecule can be repeatedly photoactivated and leads each time to cell-lethal events, that are the generation of singlet molecular oxygen or radicals.
- the half-life of singlet oxygen is such that the target cell is affected without the opportunity for migration of the lethal singlet oxygen to neighbouring healthy tissue cells.
- Singlet oxygen molecules target microorganism cell wall, or destroy intracellular structures, resulting in destruction of the target cell, without affecting chemical bonds in the cell DNA, at least at the doses which provide a complete photoinactivation.
- Destruction of target cell tissue commences promptly upon irradiation of the phthalocyanine compounds and ceases abruptly when irradiation is stopped and, due to the non interference with DNA, a development of resistance in microorganisms is unlikely.
- Photodynamic therapy with the compounds of the present invention is therefore selective and minimally toxic to healthy tissues.
- the produced singlet oxygen molecules that do not react rapidly with neighbouring molecules rapidly decay.
- a variety of phototherapy and irradiation methodologies are known to those skilled in the art and can be used with the phthalocyanine metal chelating derivatives of the present invention.
- the time and duration of therapy and repetition of the irradiation treatment can be selected by the physician, according to known photodynamic therapy criteria.
- the dosage of the phthalocyanine and the metal chelating compound in the present compositions may be varied, according to the size and location of the target tissues which are to be destroyed and the method of administration.
- the dosage will be in the range between 0.1 and 20 mg of phthalocyanine compound per kilogram of body weight per day, more preferably in the range between 0.1 and 5.0 mg/kg.
- the phthalocynine dosage will be in the range between 0.1 and 100 ⁇ g of compound per cm 2 of tissue, more preferably in the range between 1 and 10 ⁇ g/cm 2 .
- the metal chelating compounds of the present invention may be administered in an amount ranging between 0.01 and 100 mg of the chelating compound per kilogram of body weight per day, and preferably in an amount ranging from 0.1 to 10 mg/Kg per day, in case of systemic administration, while a dosage between 0.1 and 100 ⁇ g/cm 2 per day, preferably in an amount ranging from 1 to 20 ⁇ g/cm 2 , will be used in case of topical deposition.
- irradiation generally takes place not more than four days after systemic administration of the phthalocyanine compound.
- phototherapy begins approximately 10 hours to 24 hours after systemic administration of the photodynamic therapy agent.
- radiation therapy can commence immediately after topical application of the phthalocyanine or at any desired time up to 24 hours later.
- Systemic application for treatment of dermatological diseases is followed by radiation usually 15 to 24 hours after systemic administration of the PDT agent.
- Exposure to non therapeutic light sources should be avoided immediately following phototherapy, to minimize light toxicity. Appropriate protection of the patient can be used, to limit the area affected by phototherapy.
- Light sources suitable for the use in PDT are well known in the art and may vary from white light sources associated with appropriate filters to lasers tuned to the right wavelength. As noted above, preferred wavelengths are from 600 to 950 nm, preferably from about 650 to about 750 nm.
- the total amount of light which is applied to the affected area will vary with the treatment method used and with the location of the lesion. Generally, the amount of light is in the range of about 50 to 1000 J cm "2 , preferably in the range of 100 to 350 J cm "2 .
- the present pharmaceutical compositions show valuable photodynamic characteristics and higher than the photosensitising agents previously described; these properties make them useful in photodynamic therapy (PDT) against bacterial, fungal and viral infections, in particular against Gram negative bacteria; as well as for sterilization of blood and blood derivatives, such as platelets and erythrocytes.
- PDT photodynamic therapy
- the present compositions can be added directly to blood or blood derivatives, or previously bound to suitable matrix, according to known techniques and, thereafter, irradiated.
- EXAMPLE 1 ⁇ 2(3),9(10),16(17),23(24)-tetra[( ⁇ /-methyl-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-/7J quinolinium-8-yl)oxy)] phthalocyanine ⁇ zinc( . ll) iodide (compound 25) blue-green powder; formula: C 84 H 80 l 4 N 12 O 4 Zn; UV-Vis (DMF) ⁇ ma ⁇ (nm) 678 ( ⁇ -
- Si(IV) phthalocyanine ⁇ octaiodide (compound 28) blue-green powder; formula: C 104 H ⁇ 14 l 8 N 16 O ⁇ oSi; UV-Vis (DMF) ⁇ max (nm) 677,
- ⁇ 156.66, 153.35, 147.58, 142.06, 137.34, 136.80, 133.93, 129.74, 49.17.
- compositions of the present invention has been evaluated through their activity against the Gram negative micro-organisms Pseudomonas aeruginosa PAO-1 and E. coli ATCC 25922. These microorganisms were used in the experiments in a stationary phase of growth.
- the experimental protocol was the following:
- the cell suspensions were diluted in an appropriate medium. Addition of an aliquot of stock solution of the composition to be tested to the cell suspension up to the intended final concentrations. Incubation in dark at 37 °C for 5 minutes. Irradiation (650 ⁇ ⁇ ⁇ 850 nm; 50 ⁇ 100 mW/cm2; 1 ⁇ 10 minutes) of cell suspension for each dilution of the photosensitising composition.
- Figure 1 shows the photoinactivation of E. coli as a function of the concentration of the compound ⁇ 2,3,9,10,16,17,23, 24-octa[3-( ⁇ /, ⁇ /, ⁇ /-trimethylammonium)phenoxy] zinc(ll) phthalocyanine ⁇ octaiodide (compound 1).
- Compound 1 can afford a 4 log reduction of the initial population, but a complete sterilization of the cell suspension cannot De obtained.
- the inactivation can be performed by using lower fluence rates of light (50 mW/cm 2 ) and only 1 minute of irradiation (0.3 Jem "2 ) with 5 ⁇ M concentration is able to reduce the initial population by 4.5 log (see Figure 4).
- Another example is provided by the use of the compound ⁇ 2(3),9(10),16(17),23(24)-tetra[1 ,3-jb/s-(trimethylammonium)propyl-2-oxy] zinc(ll) phthalocyanine ⁇ octaiodide (compound 2) against E. coli with and without EDTA (see respectively Figure 5 and 5a). It is clearly shown that the presence of EDTA enables the reduction of the photosensitizer concentration necessary to sterilize the cell suspension from 20 ⁇ M to 1 ⁇ M.
- compositions as previously described may be administered by various routes, including parenteral or topical administration.
- the present compositions can be used either for topical treatment of skin or mucosae diseases, as well as for the ex vivo treatments, such as blood or blood derivatives sterilization.
- compositions according to the present invention include solutions, Jjposome or microvesicle preparations, dispersions, ointments and other suitable topical dermatological preparations, or preparations suitable for ex vivo applications.
- compositions may comprise pharmacologically acceptable diluents or excipients.
- Parenteral Solutions The photoactivatable phthalocyanines are generally used with additional solvents and adjuvants, to prepare solutions suitable for the in vivo or ex vivo administration.
- additional solvents and adjuvants A number of solvents and co-solvents, that are miscible with water and suitable surfactants, can be used to achieve solutions for ex vivo application, assimilated to parenteral solutions and formulations.
- the most important solvents in this group are ethanol, polyethylene glycols of the liquid series and propylene glycol.
- a more comprehensive listing includes dimethyl sulfoxide, ethanol, glycerin, polyethylene glycol 300 and 400, propylene glycol, sorbitol, polyoxyethylene sorbitan, fatty acid esters such as laurate, palmitate, stearate and oleate, polyoxyethylated vegetable oil, sorbitan monopalmitate, 2-pyrrolidpne, N-methyl-2- pyrrolidine, N-ethyl-2-pyrrolidine and tetrahydrofurfuryl alcohol.
- Other additives may be necessary to enhance or maintain chemical stability and physiological suitability. Examples are antidxidants, chelating agents, inert gases, buffers and isotonicifiers.
- the phthalocyanine and enhancers compounds of the present invention may be formulated for topical application in penetrating solvents or in the form of a lotion, cream, ointment or gel, containing a sufficient amount of the phthalocyanine compound to be effective for PDT.
- Suitable penetrating solvents are those which will enhance percutaneous penetration of the phthalocyanine compound.
- Solvents having this property include dimethyl sulfoxide, 1-methyl-2-pyrrolidone, Azone ® , Transcutol ® , lauric acid and esters, essential oils, propylene glycol, ethanol and PEG at various molecular weights.
- DMSO solutions containing 0-50 wt. % of water are particularly desirable.
- Liposomes are microvesicles which encapsulate a liquid within lipid or polymeric membranes; the methods of preparing liposomes for both topical and parenteral (injectable) preparations are known in the art and can be used for the purposes of the present invention.
- the present compositions having overall lipophilic characteristics may be incorporated into liposome microvesicles and used in this form for both topical and ex vivo applications.
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Abstract
Description
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Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003587378A JP2005524692A (en) | 2002-04-25 | 2003-04-17 | Antimicrobial composition comprising a metal phthalocyanine analog |
IL16480103A IL164801A0 (en) | 2002-04-25 | 2003-04-17 | Antibacterial compositions comprising metal phthalocyanines analogues |
CA2484070A CA2484070C (en) | 2002-04-25 | 2003-04-17 | Antibacterial compositions comprising metal phthalocyanine analogues |
US10/512,287 US8664382B2 (en) | 2002-04-25 | 2003-04-17 | Antibacterial compositions comprising metal phthalocyanine analogues |
AU2003224100A AU2003224100B2 (en) | 2002-04-25 | 2003-04-17 | Antibacterial compositions comprising metal phthalocyanine analogues |
ZA2004/09452A ZA200409452B (en) | 2002-04-25 | 2004-11-23 | Antibacterial compositions comprising metal phthalocyanine analogues |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02009414.0 | 2002-04-25 | ||
EP02009414A EP1356813B1 (en) | 2002-04-25 | 2002-04-25 | Antibacterial compositions comprising metal phthalocyanine analogues |
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WO2003090744A1 true WO2003090744A1 (en) | 2003-11-06 |
WO2003090744A8 WO2003090744A8 (en) | 2004-03-18 |
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PCT/EP2003/004080 WO2003090744A1 (en) | 2002-04-25 | 2003-04-17 | Antibacterial compositions comprising metal phthalocyanine analogues |
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US (1) | US8664382B2 (en) |
EP (1) | EP1356813B1 (en) |
JP (1) | JP2005524692A (en) |
CN (1) | CN1332658C (en) |
AT (1) | ATE299705T1 (en) |
AU (1) | AU2003224100B2 (en) |
CA (1) | CA2484070C (en) |
DE (1) | DE60205085T2 (en) |
DK (1) | DK1356813T3 (en) |
ES (1) | ES2244694T3 (en) |
IL (1) | IL164801A0 (en) |
SI (1) | SI1356813T1 (en) |
WO (1) | WO2003090744A1 (en) |
ZA (1) | ZA200409452B (en) |
Cited By (1)
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US20210032261A1 (en) * | 2018-04-09 | 2021-02-04 | Chemical Intelligence Limited | Antimicrobial and anticancer cationic phthalocyanine compounds |
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ITFI20050093A1 (en) | 2005-05-05 | 2006-11-06 | Molteni & C | PROCESS FOR THE PREPARATION OF CHLORIDE OF PHYTALOCYANIC DERIVATIVES INCLUDING AT LEAST A AMMONIUM QUATERNARY GROUP |
ITFI20050092A1 (en) | 2005-05-05 | 2006-11-06 | Molteni & C | PHYTALOCIANINE DERIVATIVES, PROCESS FOR THEIR PREPARATION, PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AND THEIR USE |
AU2006263834B8 (en) * | 2005-06-29 | 2011-11-17 | Molteni Therapeutics S.R.L. | Self-sterilizing products |
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EP3934691A1 (en) * | 2019-03-06 | 2022-01-12 | Molteni Therapeutics S.r.l. | Topical formulations containing phthalocyanine photosensitizers |
CN111072679B (en) * | 2020-01-16 | 2022-07-01 | 福州大学 | Non-peripheral quaternary ammonium group modified zinc phthalocyanine and preparation method and application thereof |
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- 2002-04-25 ES ES02009414T patent/ES2244694T3/en not_active Expired - Lifetime
- 2002-04-25 DK DK02009414T patent/DK1356813T3/en active
- 2002-04-25 DE DE60205085T patent/DE60205085T2/en not_active Expired - Lifetime
- 2002-04-25 SI SI200230199T patent/SI1356813T1/en unknown
- 2002-04-25 EP EP02009414A patent/EP1356813B1/en not_active Expired - Lifetime
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2003
- 2003-04-17 AU AU2003224100A patent/AU2003224100B2/en not_active Ceased
- 2003-04-17 JP JP2003587378A patent/JP2005524692A/en active Pending
- 2003-04-17 CA CA2484070A patent/CA2484070C/en not_active Expired - Lifetime
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- 2003-04-17 US US10/512,287 patent/US8664382B2/en active Active
- 2003-04-17 WO PCT/EP2003/004080 patent/WO2003090744A1/en active Application Filing
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Also Published As
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WO2003090744A8 (en) | 2004-03-18 |
SI1356813T1 (en) | 2006-02-28 |
US20050234032A1 (en) | 2005-10-20 |
DK1356813T3 (en) | 2005-12-05 |
ZA200409452B (en) | 2005-12-28 |
EP1356813B1 (en) | 2005-07-20 |
CN1332658C (en) | 2007-08-22 |
ATE299705T1 (en) | 2005-08-15 |
EP1356813A1 (en) | 2003-10-29 |
AU2003224100B2 (en) | 2006-10-05 |
ES2244694T3 (en) | 2005-12-16 |
IL164801A0 (en) | 2005-12-18 |
DE60205085D1 (en) | 2005-08-25 |
CN1649584A (en) | 2005-08-03 |
US8664382B2 (en) | 2014-03-04 |
AU2003224100A1 (en) | 2003-11-10 |
CA2484070C (en) | 2011-08-23 |
CA2484070A1 (en) | 2003-11-06 |
JP2005524692A (en) | 2005-08-18 |
DE60205085T2 (en) | 2006-04-20 |
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